Concurrent administration of prednisolone and peptide conjugated PMOs is not contra-indicated in the MDX mouse

Abstract

Duchenne muscular dystrophy (DMD) is a progressive, fatal muscle wasting disorder with a predictable course and limited treatment options. Advances in clinical care and management have almost doubled the life expectancy of affected boys over the last 2–3 decades, but do not address the primary etiology of DMD, the loss of dystrophin. Corticosteroids are effective in stabilizing muscle strength and prolonging ambulation, although the exact mechanism by which steroids slow the dystrophic process is unknown. Despite the limited therapeutic value of corticosteroids these drugs represent the best treatment option currently available, and a large proportion of DMD patients are treated with prednisone/prednisolone or deflazacort. Biological therapeutics are becoming available, and it will be important to establish whether these compounds can be safely administered to patients being treated with corticosteroids. Antisense oligomer-mediated splicing manipulation can bypass dystrophin gene lesions and is showing promise as a therapy for DMD. Intramuscular injection of RNA analogues, targeting exon 51, in DMD patients has resulted in specific exon exclusion and dystrophin expression in the treated muscle. We report that concurrent peptide-conjugated phosphorodiamidate morpholino oligomer and prednisolone administration is not contraindicated in mdx mice and that muscle physiology is improved by the combined treatment